技术领域technical field
本发明属于超声生物应用领域，涉及一种用于超声神经刺激的装置，特别涉及一种用于小动物脑功能区定位刺激的聚焦超声调控装置及方法。The invention belongs to the field of ultrasonic biological applications, and relates to a device for ultrasonic nerve stimulation, in particular to a focused ultrasonic control device and method for locating and stimulating small animal brain functional areas.
背景技术Background technique
近年来低强度聚焦超声由于非侵入性、高空间分辨率、高穿透深度的优点，作为一种神经调控手段引起了广泛关注。然而由于小动物脑体积小，颅骨薄脆，使现有超声设备对小动物脑区的刺激受限。目前，用于动物神经超声刺激实验的相关技术与装置无法兼顾无创、精准定位、超声参数和刺激深度可调。在进行清醒自由活动小动物脑区超声刺激的相关研究工作中，需头戴装置重量足够小、生物亲和性高，刺激作用位置足够精准。现有技术中采用的超声设备重量与体积较大，故不利于小动物清醒自由活动情况下的相关研究；特别是现有装置只能固定地刺激小动物脑区的某一个位置，不能实现对不同脑区位置的不同深度刺激，导致作用受限。In recent years, low-intensity focused ultrasound has attracted widespread attention as a means of neuromodulation due to its advantages of non-invasiveness, high spatial resolution, and high penetration depth. However, due to the small size of the brain of small animals and the fragility of the skull, the stimulation of the brain regions of small animals by existing ultrasound equipment is limited. At present, the relevant technologies and devices used in animal nerve ultrasonic stimulation experiments cannot take into account non-invasive, precise positioning, adjustable ultrasonic parameters and stimulation depth. In the research work related to ultrasonic stimulation of the brain regions of conscious and freely moving small animals, the weight of the head-mounted device is small enough, the bio-affinity is high, and the location of the stimulation is precise enough. The ultrasonic equipment used in the prior art has a large weight and volume, so it is not conducive to the relevant research in the case of small animals being awake and free; especially the existing devices can only stimulate a certain position in the brain area of small animals fixedly, and cannot achieve different depths of stimulation for different brain areas, resulting in limited effects.
发明内容Contents of the invention
本发明针对超声刺激脑神经功能区相关研究的技术需要，提供一种用于小动物脑功能区定位刺激的聚焦超声调控装置及方法，以克服现有技术中存在的问题，本发明可在小动物清醒自由活动情况下，对小动物脑功能区的不同位置及深度实现不同参数的超声刺激。Aiming at the technical needs of ultrasonic stimulation of brain functional areas, the present invention provides a focused ultrasonic control device and method for positioning and stimulating small animal brain functional areas to overcome the problems in the prior art. The present invention can achieve ultrasonic stimulation of different parameters for different positions and depths of small animal brain functional areas when the small animal is awake and free to move.
为达到上述目的，本发明采用如下技术方案：To achieve the above object, the present invention adopts the following technical solutions:
用于小动物脑功能区定位刺激的聚焦超声调控装置，包括连接在小动物颅骨平面上的头部固定器，头部固定器上依次连接有超声准直器和超声换能器，所述头部固定器、超声准直器和超声换能器同轴设置，且超声准直器和超声换能器之间采用可调连接；还包括能够与头部固定器连接的定位器及保护器，所述定位器用于对小动物颅骨平面进行坐标定位，所述保护器用于在非实验条件下防止小动物颅骨平面接触外界而发生感染。The focused ultrasound control device for positioning and stimulating small animal brain functional areas includes a head holder connected to the skull plane of the small animal. An ultrasonic collimator and an ultrasonic transducer are sequentially connected to the head holder. Infection occurs when the bone plane comes into contact with the outside world.
进一步地，所述超声准直器包括圆柱准直管以及设置于圆柱准直管下侧的圆锥收束管，所述圆柱准直管为带有内螺纹的空心圆柱结构，所述圆锥收束管为壁厚均匀的空心圆台结构，所述空心圆台结构的外侧均匀设置有若干第一卡柱。Further, the ultrasonic collimator includes a cylindrical collimation tube and a conical constricting tube arranged on the lower side of the cylindrical collimating tube, the cylindrical collimating tube is a hollow cylindrical structure with internal threads, the conical converging tube is a hollow circular frustum structure with uniform wall thickness, and several first clamping columns are uniformly arranged on the outside of the hollow circular frustum structure.
进一步地，所述超声换能器的底部为用于产生聚焦声波的凹球面结构，中部为用于配合连接圆柱准直管的带有外螺纹的第一空心圆柱结构，顶部为用于接线的第二空心圆柱结构。Further, the bottom of the ultrasonic transducer is a concave spherical structure for generating focused sound waves, the middle part is a first hollow cylindrical structure with external threads for matching and connecting a cylindrical collimator, and the top is a second hollow cylindrical structure for wiring.
进一步地，所述超声换能器的外侧设置有刻度。Further, a scale is provided on the outside of the ultrasonic transducer.
进一步地，所述头部固定器整体为空心结构，且所述头部固定器下端为倒圆角结构，上端设置有与第一卡柱配合连接的若干卡槽。Further, the head holder is a hollow structure as a whole, and the lower end of the head holder is a rounded structure, and the upper end is provided with a plurality of card slots that are mated and connected with the first post.
进一步地，所述定位器的形状与圆锥收束管一致，且所述定位器的中部设置有用于配合脑立体定位仪对小动物颅骨平面进行坐标定位的空心圆柱结构，所述定位器的外侧设置有与卡槽配合连接的若干第二卡柱。Further, the shape of the locator is consistent with the conical constricting tube, and the middle part of the locator is provided with a hollow cylindrical structure for coordinating with the stereotaxic instrument to coordinate the plane of the skull of small animals, and the outer side of the locator is provided with a plurality of second clamping posts that are connected with the slots.
进一步地，所述保护器的形状与圆锥收束管一致，且所述保护器为实心结构，保护器的外侧设置有与卡槽配合连接的若干第三卡柱，所述保护器的顶部设置有若干用于锁紧保护器和头部固定器的凹槽。Further, the shape of the protector is consistent with that of the conical constricting tube, and the protector is a solid structure, and the outer side of the protector is provided with a number of third clamping posts which are matched with the slots, and the top of the protector is provided with a number of grooves for locking the protector and the head holder.
进一步地，所述头部固定器下端通过离子水门汀固定在小动物颅骨表面上；所述头部固定器、超声准直器、超声换能器、定位器及保护器均采用透明光敏树脂材质。Further, the lower end of the head holder is fixed on the surface of the skull of the small animal by ionic cement; the head holder, ultrasonic collimator, ultrasonic transducer, positioner and protector are all made of transparent photosensitive resin.
进一步地，在使用时，还包括试验台，所述试验台包括用于为小动物提供活动平台的基座，基座上设置有竖杆，竖杆上铰接有横杆，横杆的一端设置有砝码，另一端设置有万向转轮，万向转轮下部通过导线与超声换能器连接。Further, when in use, it also includes a test stand. The test stand includes a base for providing a movable platform for small animals. A vertical bar is arranged on the base, and a horizontal bar is hinged on the vertical bar. One end of the horizontal bar is provided with a weight, and the other end is provided with a universal runner. The lower part of the universal runner is connected to the ultrasonic transducer through a wire.
用于小动物脑功能区定位刺激的聚焦超声调控方法，将小动物颅骨表面、头部固定器、超声准直器、超声换能器、定位器和保护器进行消毒处理，然后将头部固定器在定位器的协助下固定在小动物颅骨表面，待小动物适应后，将超声准直器连接到头部固定器上，然后将超声换能器连接到超声准直器上，通过调整超声换能器至所需超声强度，进行实验，观察到小动物脑区受刺激区域的神经元激活状态。Focused ultrasound control method for positioning stimulation of small animal brain functional areas. Disinfect the surface of the small animal skull, head holder, ultrasonic collimator, ultrasonic transducer, positioner and protector, and then fix the head holder on the surface of the small animal skull with the assistance of the positioner. After the small animal adapts, connect the ultrasonic collimator to the head holder, and then connect the ultrasonic transducer to the ultrasonic collimator. By adjusting the ultrasonic transducer to the required ultrasonic intensity, conduct experiments and observe the neurons in the stimulated area of the small animal brain area. active state.
与现有技术相比，本发明具有以下有益的技术效果：Compared with the prior art, the present invention has the following beneficial technical effects:
本发明装置将头部固定器与定位器配合定位可提高坐标精确度；较以往超声实验头部固定组件，本装置固定器和保护器为日常佩戴部分，仅在实验过程中才佩戴超声准直器和超声换能器，减小了重量与体积，达到不影响小动物自由活动的目的。The device of the present invention cooperates the positioning of the head holder and the locator to improve the coordinate accuracy; compared with the head fixing components of the ultrasonic experiment in the past, the holder and the protector of the device are part of the daily wear, and the ultrasonic collimator and ultrasonic transducer are only worn during the experiment, which reduces the weight and volume, and achieves the purpose of not affecting the free movement of small animals.
进一步地，本装置超声准直器与超声换能器通过螺纹配合可实现细调节脑区的刺激深度，通过调节圆柱准直管和圆锥收束管连接处的半径和圆锥收束管的高度进行粗调节脑区的刺激深度，较以往的刺激装置相比，本装置可满足实验中同一动物的不同深度脑区的重复刺激需求。Furthermore, the ultrasonic collimator and the ultrasonic transducer of this device can realize the fine adjustment of the stimulation depth of the brain region through thread cooperation, and the rough adjustment of the stimulation depth of the brain region by adjusting the radius of the connection between the cylindrical collimation tube and the conical constriction tube and the height of the conical constriction tube.
进一步地，本装置可根据需求匹配不同参数的超声换能器，更换操作简单，同时不影响超声声场的形状与能量传播，可以实现同一动物不同参数超声波的刺激效果对比。Furthermore, the device can match ultrasonic transducers with different parameters according to requirements, and the replacement operation is simple without affecting the shape and energy transmission of the ultrasonic sound field, and can realize the comparison of the stimulation effects of ultrasonic waves with different parameters on the same animal.
进一步地，本装置通过卡柱和卡槽依次同轴连接超声准直器和头部固定器进行超声作用，通过螺纹连接超声准直器和超声换能器，连接便捷，对小动物应激程度小。Further, the device sequentially connects the ultrasonic collimator and the head holder coaxially through the clamping column and the clamping groove to perform ultrasonic action, and connects the ultrasonic collimator and the ultrasonic transducer through threads, which is convenient in connection and less stressful to small animals.
进一步地，整套装置均选用透明生物亲和性的光敏树脂材质，降低了装置对于小动物暴露脑区的压迫和感染，弥补了超声作用小型动物脑区中超声换能器过大、脑组织暴露感染率高等缺陷，满足超声刺激的反复操作需求。Furthermore, the entire device is made of transparent bio-affinity photosensitive resin material, which reduces the pressure and infection of the device on the exposed brain area of small animals, makes up for the shortcomings of the ultrasonic transducer in the brain area of small animals exposed to ultrasound, and the high infection rate of brain tissue, and meets the repeated operation requirements of ultrasonic stimulation.
进一步地，本装置采用试验台配合使用，通过使用极细导线，与装有万向转轮的实验台配合使用，大大减轻了超声工作时小动物头部负重，另外万向转轮也可以避免导线缠绕。Furthermore, this device is used in conjunction with a test bench. By using ultra-thin wires, it is used in conjunction with a test bench equipped with a universal wheel, which greatly reduces the load on the head of small animals during ultrasonic work. In addition, the universal wheel can also avoid wire winding.
附图说明Description of drawings
说明书附图用来提供对本发明的进一步理解，构成本发明的一部分，本发明的示意性实施例及其说明用于解释本发明，并不构成对本发明的不当限定。The accompanying drawings in the description are used to provide a further understanding of the present invention and constitute a part of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations to the present invention.
图1为本发明装置的整体图；Fig. 1 is the whole figure of device of the present invention;
图2为本发明超声准直器结构图，其中(a)为立体图，(b)为剖视图；Fig. 2 is a structural diagram of an ultrasonic collimator of the present invention, wherein (a) is a perspective view, and (b) is a sectional view;
图3为本发明定位器结构图，其中(a)为立体图，(b)为剖视图；Fig. 3 is a structural diagram of the positioner of the present invention, wherein (a) is a perspective view, and (b) is a cross-sectional view;
图4为本发明保护器结构图，其中(a)为立体图，(b)为剖视图；Fig. 4 is a structural diagram of the protector of the present invention, wherein (a) is a perspective view, and (b) is a cross-sectional view;
图5为本发明装置的实验示意图。Fig. 5 is an experimental schematic diagram of the device of the present invention.
其中，1、小动物颅骨平面，2、头部固定器，3、超声准直器，4、超声换能器，5、定位器，6、保护器，12、卡槽，13、第一卡柱，31、圆锥收束管，32、圆柱准直管，111、小动物脑区，7、试验台。Among them, 1. Small animal skull plane, 2. Head immobilizer, 3. Ultrasonic collimator, 4. Ultrasonic transducer, 5. Positioner, 6. Protector, 12. Card slot, 13. The first clamping column, 31. Conical constricting tube, 32. Cylindrical collimating tube, 111. Small animal brain area, 7. Test bench.
具体实施方式Detailed ways
在本发明的描述中，需要理解的是，术语“上”、“下”、“左”、“右”、“前”、“后”、“中心”、“竖直”、“水平”、“顶”、“底”、“内”、“外”、“两侧”、“一侧”、“内侧”、“外侧”等指示方位或者位置关系的词，是基于附图所示的方位或者位置关系，而不是实际所特定的位置，因此不能理解为对本发明的限制，下面结合附图对本发明实施例做详细描述：In the description of the present invention, it should be understood that the terms "upper", "lower", "left", "right", "front", "rear", "center", "vertical", "horizontal", "top", "bottom", "inner", "outer", "both sides", "one side", "inner side", "outer side" and other words indicating orientation or positional relationship are based on the orientation or positional relationship shown in the accompanying drawings, rather than the actual specific position, so they cannot be interpreted as limitations on the present invention. Accompanying drawing describes in detail the embodiment of the present invention:
参见图1至图5，一种用于小动物脑功能区定位刺激的聚焦超声调控装置，包括依次同轴连接在小动物颅骨表面1上的头部固定器2、超声准直器3和超声换能器4，还包括能够与头部固定器2连接的定位器5及保护器6，所述定位器5用于对小动物颅骨平面1进行坐标定位，所述保护器6用于在非实验条件下防止小动物颅骨平面1接触外界而发生感染。Referring to FIGS. 1 to 5 , a focused ultrasound control device for locating and stimulating small animal brain functional areas includes a head holder 2, an ultrasonic collimator 3 and an ultrasonic transducer 4 coaxially connected to the surface of the small animal skull 1 in sequence, and also includes a positioner 5 and a protector 6 that can be connected to the head holder 2. The positioner 5 is used for coordinate positioning of the small animal skull plane 1, and the protector 6 is used to prevent the small animal skull plane 1 from contacting the outside world and causing infection under non-experimental conditions.
所述的超声准直器3包括圆锥收束管31和圆柱准直管32两部分，圆柱准直管32内部为螺纹结构；圆锥收束管31用于超声波的约束，圆柱准直管32用于形成平面波并输出；通过粗调圆锥收束管31与圆柱准直管32连接位置的半径和圆锥收束管31的高度，细调超声换能器4和超声准直器3的螺纹配合位置，可以控制超声作用于小动物的不同深度脑区。The ultrasonic collimator 3 includes two parts, a conical converging tube 31 and a cylindrical collimating tube 32. The interior of the cylindrical collimating tube 32 is a threaded structure; the conical converging tube 31 is used for the restraint of ultrasonic waves, and the cylindrical collimating tube 32 is used to form a plane wave and output it; by roughly adjusting the radius of the connection position between the conical converging tube 31 and the cylindrical collimating tube 32 and the height of the conical converging tube 31, and fine-tuning the threaded position of the ultrasonic transducer 4 and the ultrasonic collimator 3, the ultrasound can be controlled to act on different depths of small animals brain area.
所述的头部固定器2整体为空心结构；下端为倒圆角结构，上端设有卡槽12；其下端通过离子水门汀粘接在小动物颅骨平面1上；上端的卡槽12可分别与超声准直器3、定位器5和保护器6通过第一卡柱13、第二卡柱和第三卡柱连接。The head holder 2 is a hollow structure as a whole; the lower end is a rounded structure, and the upper end is provided with a card slot 12; its lower end is bonded to the small animal skull plane 1 through ionic cement; the card slot 12 at the upper end can be respectively connected with the ultrasonic collimator 3, the positioner 5 and the protector 6 through the first post 13, the second post and the third post.
所述的超声换能器4上具有刻度，用于螺旋深度调节；底部为凹球面结构，用于发射聚焦超声；顶部为空心圆柱结构，用于接线；中部为带有螺纹的空心圆柱结构，与圆柱准直管32通过螺纹连接固定。The ultrasonic transducer 4 has a scale for adjusting the depth of the spiral; the bottom is a concave spherical structure for emitting focused ultrasound; the top is a hollow cylindrical structure for wiring; the middle is a hollow cylindrical structure with threads, which is fixed with the cylindrical collimator 32 through threaded connections.
所述的定位器5形状与圆锥收束管31相同，但中部为空心圆柱结构，与头部固定器2连接后，在脑立体定位仪协助下定位。The shape of the locator 5 is the same as that of the conical constricting tube 31, but the middle part is a hollow cylindrical structure. After being connected with the head holder 2, it is positioned with the assistance of a brain stereotaxic instrument.
所述的保护器6形状与定位器5相同，但其整体为实心结构，顶部为凹槽结构；在未进行实验时，可通过镊子和凹槽结构配合使保护器6与头部固定器2连接锁紧，防止小动物颅骨平面1接触外界而发生感染。The shape of the protector 6 is the same as that of the locator 5, but it is a solid structure as a whole, and the top is a groove structure; when the experiment is not carried out, the protector 6 can be connected and locked with the head holder 2 through the cooperation of the tweezers and the groove structure, so as to prevent the small animal skull plane 1 from contacting the outside world and causing infection.
所述的头部固定器2、超声准直器3、超声换能器4、定位器5和保护器6，均采用透明光敏树脂材质，降低了该装置对于小动物暴露脑区的压迫和感染风险。The head holder 2, ultrasonic collimator 3, ultrasonic transducer 4, positioner 5 and protector 6 are all made of transparent photosensitive resin, which reduces the pressure and infection risk of the device on the exposed brain area of small animals.
本发明在使用时，还包括试验台7，所述试验台7包括用于为小动物提供活动平台的基座，基座上设置有竖杆，竖杆上铰接有横杆，横杆的一端设置有砝码，另一端设置有万向转轮，万向转轮下部通过导线与超声换能器4连接。When the present invention is in use, it also includes a test stand 7. The test stand 7 includes a base for providing a movable platform for small animals. A vertical bar is arranged on the base, and a horizontal bar is hinged on the vertical bar. One end of the horizontal bar is provided with a weight, and the other end is provided with a universal runner. The lower part of the universal runner is connected to the ultrasonic transducer 4 through a wire.
以下给出本发明的具体实施例，需要说明的是本发明并不局限于以下具体实施例，凡在本申请技术方案基础上做的等同变换均落入本发明的保护范围。Specific embodiments of the present invention are provided below, and it should be noted that the present invention is not limited to the following specific embodiments, and all equivalent transformations done on the basis of the technical solutions of the present application all fall within the protection scope of the present invention.
本实施例采用小鼠作为实验对象。In this embodiment, mice are used as experimental subjects.
具体实施例1：Specific embodiment 1:
首次实验前，首先将对小动物颅骨表面1和包括头部固定器2、超声准直器3、超声换能器4、定位器5和保护器6在内的超声作用装置进行消毒处理；其次对目标的小动物颅骨平面1进行手术处理，将头部固定器2在定位器5的协助下通过离子水门汀固定在小动物颅骨表面1上，待小鼠适应后进行实验。Before the first experiment, the small animal skull surface 1 and the ultrasonic device including the head holder 2, ultrasonic collimator 3, ultrasonic transducer 4, positioner 5, and protector 6 were first disinfected; secondly, the target small animal skull plane 1 was surgically treated, and the head holder 2 was fixed on the small animal skull surface 1 by ion cement with the assistance of the positioner 5, and the experiment was carried out after the mice adapted.
首次实验时，将超声调节到实验所需超声强度，选用高度为2mm的圆锥收束管31和直径为6.2mm的圆柱准直管32组成的超声准直器3，通过螺纹连接在一起，再将超声准直器3通过第一卡柱13和卡槽12连接到头部固定器2上，进行实验，实验观察到小动物脑区111受刺激区域的神经元被激活。In the first experiment, the ultrasound was adjusted to the ultrasonic intensity required for the experiment, and the ultrasonic collimator 3 composed of a conical constrictor tube 31 with a height of 2 mm and a cylindrical collimator tube 32 with a diameter of 6.2 mm was selected, connected together by threads, and then the ultrasonic collimator 3 was connected to the head holder 2 through the first clamping column 13 and the clamping groove 12, and the experiment was carried out. The neurons in the stimulated area of the brain region 111 of the small animal were observed to be activated in the experiment.
首次实验后，依次将超声准直器3和超声换能器4取下，并将保护器6通过第三卡柱和卡槽12连接到头部固定器2上，并利用镊子通过保护器6上的凹槽结构锁紧，整理收纳所有实验设备。After the first experiment, the ultrasonic collimator 3 and the ultrasonic transducer 4 were removed in turn, and the protector 6 was connected to the head holder 2 through the third post and the slot 12, and the tweezers were used to lock through the groove structure on the protector 6, and all the experimental equipment was organized and stored.
优选的，在本发明实施过程中，可以通过试验台7进行试验，通过竖杆、横杆以及配合的砝码和外向转轮对小鼠头部的装置减重，使小鼠能够在基座上的笼子中可以自由活动，且不会对导线形成缠绕，笼子上部设有开口。Preferably, during the implementation of the present invention, the test can be carried out by the test bench 7, and the weight of the mouse head can be reduced by vertical bars, cross bars, matched weights and outward runners, so that the mice can move freely in the cage on the base, and the wires will not be entangled. The upper part of the cage is provided with an opening.
具体实施例2：Specific embodiment 2:
二次和多次实验，只需用镊子取下保护器6，然后将超声调节到目标参数，选用合适尺寸的超声准直器3，通过螺纹将超声换能器4和超声准直器3连接在一起，再将超声准直器3通过第一卡柱13和卡槽12连接到头部固定器2上，进行实验。实验完成后，依次将超声准直器3和超声换能器4取下，并将保护器6通过第三卡柱和卡槽12连接到头部固定器2上，并利用镊子通过保护器6上的凹槽锁紧，整理收纳所有实验设备。For secondary and multiple experiments, it is only necessary to remove the protector 6 with tweezers, then adjust the ultrasound to the target parameters, select an ultrasonic collimator 3 of suitable size, connect the ultrasonic transducer 4 and the ultrasonic collimator 3 through threads, and then connect the ultrasonic collimator 3 to the head holder 2 through the first clamping post 13 and the card slot 12, and conduct the experiment. After the experiment is completed, the ultrasonic collimator 3 and the ultrasonic transducer 4 are removed in turn, and the protector 6 is connected to the head holder 2 through the third post and the slot 12, and the tweezers are used to lock through the groove on the protector 6 to organize and store all the experimental equipment.
优选的，也可以采用试验台7进行辅助操作。Preferably, the test bench 7 can also be used for auxiliary operations.
以上内容仅为说明本发明的技术思想，不能以此限定本发明的保护范围，凡是按照本发明提出的技术思想，在技术方案基础上所做的任何改动，均落入本发明权利要求书的保护范围之内。The above content is only to illustrate the technical idea of the present invention, and cannot limit the scope of protection of the present invention. Any changes made on the basis of the technical solution according to the technical idea proposed in the present invention, all fall within the protection scope of the claims of the present invention.
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| CN202110867011.XACN113559425B (en) | 2021-07-29 | 2021-07-29 | Focused ultrasound control device and method for positioning and stimulating brain functional areas of small animals |
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| CN202110867011.XACN113559425B (en) | 2021-07-29 | 2021-07-29 | Focused ultrasound control device and method for positioning and stimulating brain functional areas of small animals |
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